OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Voclosporin – Lupkynis®

DRUG CLASS

Immunosuppressive Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULAS AND STRUCTURES

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Voclosporin	515814-01-4	C63-H111-N11-O12
Cyclosporine	59865-13-3	C62-H111-N11-O12

ANNOTATED BIBLIOGRAPHY

References updated: 30 August 2021

Abbreviations used: eGFR, estimated glomerular filtration rate.

• Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 673-708.

  (Expert review of hepatotoxicity published in 1999; voclosporin is not mentioned but cyclosporine is discussed; cyclosporine therapy is associated with a high rate of cholestatic liver enzyme elevations ranging from 4-86% and has been linked to occasional instances of cholestatic hepatitis, some features of which are reproducible in animal models).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2021/213716Orig1s000MultidisciplineR.pdf.

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA integrated review of the voclosporin application for safety and efficacy which mentions [pages 202-3] that mean values of ALT, Alk P, GGT and bilirubin remained in the normal range although mean levels of Alk P and bilirubin increased slightly during therapy; the rate of ALT or AST elevations above 3 times ULN was similar in incidence to that in placebo recipients [3% vs 2%] and were transient and asymptomatic, except for one case of liver injury with jaundice in a patient with pulmonary tuberculosis who was receiving antimycobacterial therapy).
• Bissonnette R, Papp K, Poulin Y, Lauzon G, Aspeslet L, Huizinga R, Mayo P, et al. ISA247 Psoriasis Study Group. A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2006;54:472–8. [PubMed: 16488299]

  (Among 201 adults with plaque psoriasis treated with voclosporin [0.5 mg/kg or 1.5 mg/kg] or placebo daily for 12 weeks, improvements in psoriasis occurred in 15% and 45% of voclosporin vs 0% of placebo recipients, and adverse events more frequent with voclosporin included nausea, diarrhea, abdominal pain, vomiting, dizziness, and paresthesias, while there were “no significant changes” in hepatic laboratory features).
• Busque S, Cantarovich M, Mulgaonkar S, Gaston R, Gaber AO, Mayo PR, Ling S, et al. PROMISE Investigators. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant. 2011;11:2675–84. [PubMed: 21943027]

  (Among 334 patients undergoing renal transplantation treated with either voclosporin [3 doses] or tacrolimus for 24 weeks, rates of biopsy proven acute cellular rejection were comparable in the 4 groups as were adverse event rates).
• Rovin BH, Solomons N, Pendergraft WF 3rd, Dooley MA, Tumlin J, Romero-Diaz J, Lysenko L, et al. AURA-LV Study Group. A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int. 2019;951:219–231. [PubMed: 30420324]

  (Among 265 patients with active lupus nephritis treated with voclosporin [23.7 mg or 39.5 mg] vs placebo twice daily for 48 weeks, complete renal responses occurred in 49% and 40% vs 24%, while serious adverse events were more frequent with voclosporin [28% and 25% vs 16%] as were infections [12% and 14% vs 8%] and all-cause mortality [11% and 2.3% vs 1%]).
• Heo YA. Voclosporin: first approval. Drugs. 2021;81:605–610. [PMC free article: PMC8010786] [PubMed: 33788181]

  (Review of the mechanism of action, history of development, clinical efficacy and safety of voclosporin shortly after its approval for use in lupus nephritis mentions common adverse events as being transient decline in GFR, hypertension, headache, anemia and cough).
• Rovin BH, Teng YKO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, Gibson K, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021;397(10289):2070–2080. [PubMed: 33971155]

  (Among 457 patients with active lupus nephritis treated with voclosporin [23.7 mg] or placebo twice daily for 52 weeks, “complete renal response” rates were higher with voclosporin [41% vs 23%], while serious adverse events were similar [21% vs 21%] and deaths were fewer in number [1 vs 5]).
• Voclosporin (Lupkynis) for lupus nephritis. Med Lett Drugs Ther. 2021;63(1631):134–6. [PubMed: 34544103]

  (Concise summary of the mechanism of action, clinical efficacy, safety and costs of voclosporin, a calcineurin inhibitor approved for lupus nephritis mentions that therapy can increase the risk of bacterial, viral and fungal infections, can prolong the QT interval, and can cause hyperkalemia and neurotoxicity; no mention of ALT elevations or hepatotoxicity).